This invention relates to a trifluorohydroxyaromatic acid and preparetion thereof, more particularly to a novel substance 2,4,5-trifluoro-3-hydroxybenzoic acid useful as the synthetic intermediate for the quinolone carboxylic acid type antibacterial agent and a process for producing the same, and further to a process for preparing 3,5,6-trifluoro-4-hydroxyphthalic acid useful as the precursor of 2,4,5-trifluoro-3-hydroxybenzoic acid.
In the prior art, as the synthetic antibacterial agent, there have been known developed nalidixic acid represented by the following formula: ##STR2## pipemidic acid represented by the following formula: ##STR3## piromidic acid represented by the following formula: ##STR4## Norfloxacin represented by the following formula: ##STR5## etc., and have been provided for therapy of various infectious diseases.
Further, as the compound which improves various characteristics of the above antibacterial agents, quinolone carboxylic acid type antibacterial agents, having oxygen atom at the 8-position have been developed (for example, Japanese Patent Publication No. 11955/1986).
However, a large number of steps are required for synthesis of a quinolone carboxylic acid derivative having oxygen atom at the 8-position, and it has been desired to shorten the preparation steps.
2,4,5-Trifluoro-3-hydroxybenzoic acid represented by the following formula (I) may be considered to be useful as the synthetic intermediate for the above quinolone carboxylic acid derivative: ##STR6##
However, even if a nucleophilic reagent such as RO.sup.- or OH.sup.- may be reacted with 2,3,4,5-tetrafluorobenzoic acid, no nucleophilic reaction to the meta-position of the carboxylic group occurs, but the reaction occurs all selectively with the para-position and the ortho-position to give no 2,4,5-trifluoro-3-hydroxybenzoic acid. Also, according to other methods, no 2,4,5-trifluoro-3-hydroxybenzoic acid has been obtained.
It can be expected that 3,5,6-trifluoro-4-hydroxyphthalic acid is useful as the precursor of 2,4,5-trifluoro-3-hydroxybenzoic acid.
A process for preparing 3,5,6-trifluoro-4-hydroxyphthalic acid used here as the starting material is described in Osadchii, S. A., Bakahash, V. A.; Zh. Org. Khim., Vol. 6 (8), p. 1636 (1970) (Chemical Abstract, 73, 109544p). According to this litrature, when tetrafluorophthalic anhydride and pentafluorophenylacetic acid are reacted in triethylamine-acetic anhydride, a triethylamine salt of 5-hydroxy-4,6,7-trifluoro-3-(pentafluorobenzylidene)phthalide is obtained. And, by treatment of the by-products of this reaction, 3,5,6-trifluoro-4-hydroxyphthalic acid is obtained.
However, this process obtains 3,5,6-trifluoro-4-hydroxyphthalic acid as the accompanying reaction product, its yield is low and also the reactions are cumbersome.
Also, Ishikawa, Suzuki, Tanabe, et al. report a method for synthesis of dimethyl 3,5,6-trifluoro-4-methoxyphthalate in Journal of Chemical Society of Japan, p. 200 (1976). From this compound, according to a known method (for example, after converted to 3,5,6-trifluoro-4-methoxyphthalic acid by hydrolysis with an aqueous alkali solution, reacted with a strong acid such as hydrobromic acid), 3,5,6-trifluoro-4-hydroxyphthalic acid can be obtained.
However, this method obtains dimethyl 3,5,6-trifluoro-4-methoxyphthalate by the reaction after tetrafluorophthalic acid is once converted to a methyl ester, and the three methyl groups are required to be eliminated for obtaining the objective 3,5,6-trifluoro-4-hydroxyphthalic acid. Thus, it can be hardly said to be a rational method.
The present inventors, in view of the state of the art as described above, have intensively studied about an industrial process for preparing 2,4,5-trifluoro-3-hydroxybenzoic acid and its precursor, 3,5,6-trifluoro-4-hydroxyphthalic acid to accomplish the present invention.